title: Obesity-dependent cannabinoid modulation of proliferation in adult neurogenic regions.
abstract: Endocannabinoid signalling participates in the control of neurogenesis, especially after brain insults. Obesity may explain alterations in physiology affecting neurogenesis, although it is unclear whether cannabinoid signalling may modulate neural proliferation in obese animals. Here we analyse the impact of obesity by using two approaches, a high-fat diet (HFD, 60% fat) and a standard/low-fat diet (STD, 10% fat), and the response to a subchronic treatment with the cannabinoid receptor type 1 (CB1) inverse agonist AM251 (3 mg/kg) on cell proliferation of two relevant neurogenic regions, namely the subventricular zone in the striatal wall of the lateral ventricle (SVZ) and the subgranular zone of the dentate gyrus (SGZ), and also in the hypothalamus given its role in energy metabolism. We found evidence of an interaction between diet-induced obesity and CB1 signalling in the regulation of cell proliferation. AM251 reduced caloric intake and body weight in obese rats, as well as corrected plasma levels of cholesterol and triglycerides. AM251 is shown, for the first time, to modulate cell proliferation in HFD-obese rats only. We observed an increase in the number of 5-bromo-2-deoxyuridine-labelled (BrdU+) cells in the SGZ, but a decrease in the number of BrdU+ cells in the SVZ and the hypothalamus of AM251-treated HFD rats. These BrdU+ cells expressed the neuron-specific βIII-tubulin. These results suggest that obesity may impact cell proliferation in the brain selectively, and provide support for a role of CB1 signalling regulation of neurogenesis in response to obesity.
authors.affiliation: Laboratorio de Medicina Regenerativa, Hospital Carlos Haya, Fundación IMABIS, Avda. Carlos Haya 82, Pabellón de Gobierno, 29010 Málaga, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Rivera
authors.forename: Yanina
authors.initials: Y
authors.lastname: Romero-Zerbo
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Pavón
authors.forename: Antonia
authors.initials: A
authors.lastname: Serrano
authors.forename: María-Dolores
authors.initials: MD
authors.lastname: López-Ávalos
authors.forename: Manuel
authors.initials: M
authors.lastname: Cifuentes
authors.forename: Jesús-Mateos
authors.initials: JM
authors.lastname: Grondona
authors.forename: Francisco-Javier
authors.initials: FJ
authors.lastname: Bermúdez-Silva
authors.forename: Pedro
authors.initials: P
authors.lastname: Fernández-Llebrez
authors.forename: Fernando R
authors.initials: FR
authors.lastname: de Fonseca
authors.forename: Juan
authors.initials: J
authors.lastname: Suárez
authors.forename: Margarita
authors.initials: M
authors.lastname: Pérez-Martín
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D049109:Cell Proliferation; D002784:Cholesterol / Q000097:blood; D004041:Dietary Fats / Q000008:administration & dosage; D002149:Energy Intake / Q000187:drug effects; D005260:Female; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D055495:Neurogenesis / Q000502:physiology*; D009765:Obesity / Q000503:physiopathology*; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D063385:Cannabinoid Receptor Modulators; D004041:Dietary Fats; D007328:Insulin; D020738:Leptin; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D014280:Triglycerides; C103505:AM 251; D002784:Cholesterol